The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits.

Introductions: Spinach (Amaranthus hybridus) is a green vegetable containing 380 μg/100 g of vitamin K, while warfarin serves as an antagonist in inhibiting vitamin K epoxide reductase subunit C1 (VKORC). In this context, the co-administration of warfarin and spinach is frequently encountered among Indonesian patients, potentially leading to drug-food interactions. This study aimed to investigate the effect of concomitant administration of spinach on the pharmacokinetic and pharmacodynamic profile of warfarin in New Zealand White rabbits.

Methods: A total of 24 New Zealand White rabbits weighing about 1.5-2 kg were used in this study. For 16 days, these rabbits were given oral warfarin at a dose of 0.4 mg/kg BW by 10.00 am. Subsequently, 3 mL of blood samples were withdrawn in the lateral vein of the ear on the 13th and 16th days. The Prothrombin Time-International Normalized Ratio (PT-INR) is used to evaluate the pharmacodynamic profile, while the plasma concentration of S(R)-warfarin (Cp (AV)), half-life (t_½), area under the curve (AUC), volume of distribution (Vd), and clearance (C_L) are analyzed to determine the pharmacokinetic effects of warfarin.

Results: In the Fluconazole (FZ) group, there was a significant increase in the area under the curve (AUC) at maximum concentration (Cmax) after treatment, with a p-value of < 0.05. In the Amaranthus hybridus dose 1 (AH-1) and Amaranthus hybridus dose 2 (AH-2) groups, AUC and plasma drug concentration (Cp (AV)) were higher after treatment but the results of statistical analysis were not significant.

Conclusion: There was no pharmacokinetic or pharmacodynamic interaction between spinach (Amaranthus hybridus) and warfarin. Additionally, patients subjected to warfarin therapy could consume spinach with a recommended portion size below 100 grams per day.